Makoto Gozawa

The Effect of Photocoagulation in Ischemic Areas to Prevent Recurrence of Diabetic Macular Edema After Intravitreal Bevacizumab Injection

PURPOSE This study aimed to investigate whether targeted retinal photocoagulation (TRP) for nonperfused areas (NPAs) could have a preventive effect on the recurrence of diabetic macular edema (DME) after intravitreal injection of bevacizumab (IVB). METHODS Eyes in the IVB group received 1.25 mg IVB, and eyes in the IVB+TRP group received 1.25 mg IVB combined with TRP of NPAs. Two weeks before IVB administration, grid/focal photocoagulation (PC) had been performed in both groups. After IVB treatment, the best corrected visual acuity (BCVA) and central retinal thickness (CRT), determined by optical coherence tomography, were measured every month for 6 months. RESULTS Fifty-two patients with DME were enrolled and randomized to an IVB group (n = 26) and an IVB+TRP group (n = 26). After IVB, the CRT decreased temporally, and the CRT significantly increased at 2 months and thereafter in the IVB group but did not increase significantly in the IVB+TRP group. Maximum increase in CRT after IVB was significantly correlated with the width of NPAs in the IVB group (P = 0.0368), but not in the IVB+TRP group. Best corrected visual acuity in the IVB+TRP group was significantly better than that in the IVB group 5 and 6 months after treatment (P < 0.05). CONCLUSIONS Targeted retinal photocoagulation for NPAs was effective to maintain the reduced CRT after grid/focal PC and IVB for patients with DME. These results suggest that retinal ischemia is associated with the pathogenesis of recurrence of DME after IVB. ( www.umin.ac.jp/ctr number, UMIN000007566.).

Comparison of the Inverted Internal Limiting Membrane Flap Technique and the Internal Limiting Membrane Peeling for Macular Hole with Retinal Detachment

Purpose To evaluate the efficacy of the inverted internal limiting membrane (ILM) flap technique in vitrectomy for macular hole (MH) with retinal detachment (RD) compared with vitrectomy using ILM peeling. Methods A retrospective case series study was performed. Twenty-two eyes of 22 patients who underwent vitrectomy for MH with RD and followed-up more than 12 months after the surgery were included in this study. We retrospectively reviewed the medical records of patients who underwent vitrectomy with inverted ILM flap technique or vitrectomy with ILM peeling. Ten patients who had been treated vitrectomy with inverted ILM flap technique, and 12 patients who had been treated vitrectomy with ILM peeling were analyzed. We evaluated changes in best-corrected visual acuity (BCVA) before and after surgery, closing rates of MH, and retinal reattachment rates and compared between both groups. Results MH was closed and RD was reattached postoperatively in 9 eyes (90%) in the inverted ILM flap group. In the ILM peeling group, the MH was closed in 4 eyes (33.3%) and the retinas were reattached in 6 eyes (50%) after surgery. Significant improvement in BCVA after surgery (P = 0.0017) was only found in the inverted ILM flap group. Conclusions Higher rates of closed MH and retinal reattachment, and small but significant improvement in BCVA were found in the inverted ILM flap group. Based on our data, the inverted ILM flap technique may be useful in vitrectomy for MH with RD.

The effect of triamcinolone acetonide or bevacizumab on the levels of proinflammatory cytokines after retinal laser photocoagulation in pigmented rabbits.

Although laser photocoagulation is a gold standard for the treatment of retinal ischemic diseases, thermal burn induces the inflammation and the progression of macular edema. To prevent this complication, combination therapy using anti-vascular endothelial growth factor (VEGF) drugs or steroids is clinically utilized, however the mechanisms are still unclear. In this study, we aimed to evaluate the changes in inflammatory and angiogenic cytokine levels in aqueous humor and vitreous body after intravitreal injection of bevacizumab (IVB) or triamcinolone (IVTA), as well as sub-Tenon injection of triamcinolone (STTA) after retinal laser photocoagulation in rabbits. Pigmented rabbits were treated with retinal laser photocoagulation and divided into 4 groups, namely Control (no additional treatment), IVB, IVTA or STTA accordingly. Samples of vitreous and aqueous humor were collected on post-treatment days 0, 1, 7 and 14. The levels of intraocular VEGF, interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemotactic protein-1 (MCP-1) were measured using an immunoassay. The levels of VEGF, IL-6, ICAM-1 and MCP-1 were significantly elevated 1 day after laser treatment. IVTA and STTA significantly reduced the increase in the levels of VEGF, IL-6, ICAM-1 and MCP-1, while IVB reduced that of VEGF only in aqueous humor and vitreous body. The protein amount in the aqueous humor transiently increased 1 day after laser, and was significantly prevented by IVTA or STTA but not IVB. Data showed that bevacizumab only reduced intraocular VEGF after laser, while triamcinolone suppressed both the expression of VEGF and proinflammatory cytokines. We propose that these cytokine profiles may play an important role in the pathogenesis of inflammation after photocoagulation and the underlying mechanism of treatment with anti-VEGF drug and steroids.

Comparative study of combined bevacizumab/targeted photocoagulation vs bevacizumab alone for macular oedema in ischaemic branch retinal vein occlusions

To investigate whether targeted retinal photocoagulation (TRP) of peripheral non‐perfused areas (NPAs) could prevent the recurrence of macular oedema (ME) due to branch retinal vein occlusion (BRVO) after intravitreal bevacizumab injection (IVB).

Panretinal Photocoagulation Using Short-Pulse Laser Induces Less Inflammation and Macular Thickening in Patients with Diabetic Retinopathy

We compared the effect of panretinal photocoagulation (PRP) using short-pulse laser (SPL) and conventional laser, regardless of the number of spots, in terms of their effect on the progression of diabetic macular edema (DME) and anterior flare intensity (AFI) in patients with high-risk nonproliferative diabetic retinopathy (non-PDR). Forty-two eyes of 42 patients were subjected to PRP using the conventional argon laser (Conv group) or SPL (SPL group). CRT and AFI levels in the SPL group were significantly lower than those in the Conv group (CRT at 4, 6, and 10 weeks; AFI at 6, 10, and 18 weeks). Eyes of rabbits were photocoagulated using conventional laser with 500 spots (Conv 500s), SPL with 500 spots (SPL 500s), or 1000 spots (SPL 1000s). Vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and monocyte chemotactic protein-1 (MCP-1) levels in vitreous humor were measured using an immunoassay. Compared to conventional laser, VEGF, IL-6, and MCP-1 levels were significantly lower in the SPL 1000s and SPL 500s groups. In patients with high-risk non-PDR, SPL has a greater preventive effect on the progression of DME and AFI and produces less inflammatory cytokines than conventional lasers.

Comparison of subconjunctival scarring after microincision vitrectomy surgery using 20-, 23-, 25- and 27-gauge systems in rabbits

To compare subconjunctival scarring after vitrectomy in rabbit eyes using different gauge systems by analysing anterior segment optical coherence tomography (AS‐OCT) images and histological sections.

Changes in Matrix Metalloproteinases in Diabetes Patients' Tears After Vitrectomy and the Relationship With Corneal Epithelial Disorder.

PURPOSE Previous studies indicate involvement of matrix metalloproteinases (MMPs) in the pathogenesis of diabetic keratopathy. To evaluate MMP levels in the tears of patients with diabetes, we investigated changes in MMP levels during perioperative periods and clarify the relationship with corneal epithelial disorders following vitrectomy. METHODS Matrix metalloproteinase levels in tears were measured by multiplex bead array in patients with or without diabetes who were scheduled for vitrectomy. Twenty-two patients with diabetes and proliferative diabetic retinopathy, and 20 patients with epiretinal membrane or macular hole (control group), were recruited. Changes in MMP levels during perioperative periods and the relationship with corneal epithelial disorders after vitrectomy were analyzed. RESULTS The levels of MMP-2, -9, and -10 at 1 day after surgery in the diabetic group were significantly higher than in the control group. At 1 week after surgery, MMP-10 levels in the diabetic group were significantly higher than in the control group. After vitrectomy, corneal epithelial disorders occurred in six patients in the diabetic group but not in the control group. In the diabetic group, MMP-10 levels in tears of patients with corneal epithelial disorders were significantly higher than those in patients without corneal epithelial disorders. CONCLUSIONS The MMP concentration in tears of patients with diabetes was higher than in nondiabetic patients after vitrectomy. High MMP-10 levels were observed in patients with diabetes and corneal epithelial disorders after vitrectomy. Aberrant levels of MMP-10 may cause corneal epithelial disorder after vitrectomy.

Photocoagulation of the Retinal Nonperfusion Area Prevents the Expression of the Vascular Endothelial Growth Factor in an Animal Model

Purpose The purpose of this study was to evaluate whether photocoagulation of the retinal nonperfusion area suppresses ocular vascular endothelial growth factor (VEGF) expression in a rabbit retinal vein occlusion (RVO) model. Methods The retinas of pigmented rabbits were made ischemic by a laser on the main branch of retinal veins following intravenous injection of Rose Bengal. The eyes were enucleated before treatment and at 1, 7, and 14 days after laser occlusion. VEGF protein levels in the vitreous humor, sensory retina, and retinal pigment epithelium-choroid were measured with enzyme-linked immunosorbent assay. In situ hybridization of VEGF messenger RNA was performed to detect the location of VEGF expression in the sensory retina. Results In the vitreous body, the VEGF protein level in the RVO group, but not that in the RVO + panretinal photocoagulation group, significantly increased on day 14. In the retina, the VEGF protein level in the RVO + panretinal photocoagulation group was significantly higher than that in the RVO group on day 1, but was significantly lower than that in the RVO group on days 7 and 14. In the in situ hybridization analysis, the RVO group showed a high expression of VEGF in the inner nuclear and ganglion cell layers on days 7 and 14. In contrast, VEGF expression in the RVO + panretinal photocoagulation group was strongly suppressed in both the inner nuclear and ganglion cell layers on days 7 and 14. Conclusions This study is the first using an animal RVO model to demonstrate that laser photocoagulation of the retinal nonperfusion area suppresses VEGF-A expression in the retina.

Randomized Clinical Trial for Early Postoperative Complications of Ex-PRESS Implantation versus Trabeculectomy: Complications Postoperatively of Ex-PRESS versus Trabeculectomy Study (CPETS).

We compared early postoperative complications between trabeculectomy and Ex-PRESS implantation. Enrolled patients with 39 primary open-angle or 25 exfoliative glaucoma were randomly assigned to receive trabeculectomy (trabeculectomy group) or Ex-PRESS implantation (Ex-PRESS group). Primary outcomes were early postoperative complications, including postoperative anterior chamber inflammation, frequencies of hyphema, flat anterior chamber, choroidal detachment, hypotonic maculopathy, and the change of visual acuity. The postoperative flare values in trabeculectomy group were higher than those in the Ex-PRESS group (overall, P = 0.004; and 10 days, P = 0.02). Hyphema occurred significantly more frequently in the trabeculectomy group (P = 0.0025). There were no significant differences of the other primary outcomes between the two groups. Additionally, duration of anterior chamber opening was significantly shorter in the Ex-PRESS group (P = 0.0002) and the eyes that had iris contact with Ex-PRESS tube had significantly shallower anterior chambers than did the eyes without the iris contact (P = 0.013). The Ex-PRESS implantation prevented early postoperative inflammation and hyphema in the anterior chamber and shortened the duration of anterior chamber opening. Iris contact with the Ex-PRESS tube occurred more frequently in eyes with open-angle glaucoma and shallow anterior chambers.

Prospective observational study of conjunctival scarring after phacoemulsification.

To examine whether anterior segment‐optical coherence tomography (AS‐OCT) can detect conjunctival scarring after transscleral phacoemulsification and whether temporal transscleral phacoemulsification causes scarring in the superior conjunctiva.